Kaempferol ameliorates oxidative stress injury in the retina through activating the PI3K/AKT/mTOR signaling pathway
Objective To investigate the mechanism of kaempferol in alleviating retinal oxidative stress injury.Methods ARPE-19 cells were treated with H2O2 to establish an in vitro model of retinal oxidative stress injury.The cell viability was assessed by CCK-8 assay.The apoptosis was detected by flow cytometry.Twenty-five male SD rats were randomly divided into five groups:a control group,a model group,a low-dose(12.5 mg/kg)kaempferol group,a medium-dose(25 mg/kg)kaempferol group and a high-dose(50 mg/kg)kaempferol group.Rats in the control group were kept normally,while those in the model and treatment groups were subject to acute retinal ischemia/reperfusion injury to construct a model of retinal oxidative stress injury.The intracellular activities of superoxide dismutase(SOD)and malondialdehyde(MDA)were detected,the structural integrity of the retina was observed by H-E staining.The expression of inflammatory cytokines was detected by enzyme-linked immunosorbent assay(ELISA).The expression of apoptotic autophagy and the effect of PI3K/AKT/mTOR signaling pathway were evaluated by Western blot.Results In vitro cellular experiments showed that kaempferol significantly increased the viability and decreased the apoptosis of ARPE-19 cells induced by oxidative stress,compared with the control group(P＜0.05).In vivo experiments showed that compared with the model group,kaempferol attenuated retinal oxidative stress injury;significantly decreased MDA expression and elevated SOD expression(P＜0.05);significantly decreased the secretion of vascular endothelial growth factor(VEGF)and γ-interferon(IFN-γ)and increased the secretion of interleukin-10(IL-10)(P＜0.05);and significantly enhanced the protein expression of B cell lymphoma/leukaemia-2(BCL-2),microtubule-associated protein 1A/1B-light chain 3(LC3),phosphatidylinositol 3 kinase(PI3K),phosphorylated target of rapamycin mechanism(p-mTOR)and phosphorylated serine/threonine kinase(p-AKT)and inhibited the protein expression of the antibody to the Bcl-2 cognate structural domain protein 1(Beclin1)(P＜0.05).Conclusions Kaempferol attenuates retinal oxidative stress injury by activating the PI3K/AKT/mTOR signaling pathway.
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